The isolation of stilbene derivatives, termed combretastatins, from the South African tree Combretum caffrum has been described. Many of these combretastatins were found to be cytotoxic, with combretastatin A-4 being the most potent. This compound was found to inhibit tubulin polymerization and to competitively inhibit the binding of radiolabeled colchicines to tubulin. Investigation of combretastatins revealed that combretastatin A-4 was active against multidrug resistant (MDR) cancer cell lines. Combretastatin A-4, as well as its trans isomer and a number of related substances, have been found to cause mitotic arrest in cells in culture at cytotoxic concentrations. trans-Tetrahydroxystilbene and a number of related substances were also reported to be cytotoxic agents.
2,3-Diarylacrylonitriles are also very important synthons for the synthesis of a wide spectrum of biologically active molecules. These compounds have been shown to possess spasmolytic, estrogenic, hypotensive, antioxidative, tuberculostatic, antitrichomonal, insecticidal and cytotoxic activities. Also, many natural products possessing a trimethoxybenzene ring, e.g., colchicines, and podophyllotoxin, were found to be potent cytotoxic agents and exert their antitumor properties based on their antitubulin character.
Although some compounds have shown biological activity, there remains a need for novel compounds for the treatment of disease.